Means and method for hormonal contraception

• US 20020193356A1
• Filed: 05/23/2001
• Published: 12/19/2002
• Est. Priority Date: 05/23/2001
• Status: Abandoned Application

• Current Assignee: PANTARHEI BIOSCIENCE B.V.
• Original Assignee: PANTARHEI BIOSCIENCE B.V.
• Inventors: Coelingh Bennink, Herman Jan Tijmen, Van Beek, Agatha Antonia Magdalena
• Application Number:
  US09/862,618
• Publication Number:
  US 20020193356A1
• Time in Patent Office: Days
• US Class Current: 514/169
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids

Abstract

The present invention is concerned with a kit containing a plurality of hormone units for use in a contraceptive method which consists of two alternating consecutive phases, sometimes referred to as a sequential method or sequential regimen. More particularly the present invention relates to a kit containing a plurality of daily hormone units for use in a contraceptive method which consists of two alternating consecutive phases—an estrogenic and a progestogenic phase—of administering a sequence of said hormone units to a female of childbearing capability, the plurality of daily hormone units consisting of:

a) one or more daily hormone units, for use during the estrogenic phase, containing synthetic estrogen or a combination of synthetic estrogen and biogenic estrogen in a therapeutically effective amount to inhibit ovulation and

b) at least 10 daily hormone units, for use during the progestogenic phase, containing a combination of biogenic estrogen and progestogen in a therapeutically effective amount to inhibit ovulation and to transform the endometrium from a proliferative into a secretory state.

Claims

1. A kit containing a plurality of daily hormone units for use in a contraceptive method, the plurality of daily hormone units consisting of:

a) one or more daily hormone units, for use during an estrogenic phase, containing a synthetic estrogen or a combination of synthetic estrogen and biogenic estrogen in an amount equivalent to 3-40 μ

g ethinyl estradiol and

b) at least 10 daily hormone units, for use during a progestogenic phase, containing biogenic estrogen in an amount equivalent to 0.5-5 mg 17beta-estradiol and progestogen in an amount equivalent to 30-750 μ

g levonorgestrel.

2. A kit according to claim 1, wherein the plurality of hormone units consists of 20 to 35 daily hormone units, preferably 28 daily hormone units.

3. A kit according to claim 1, wherein the units for use during the estrogenic phase also contain a biogenic estrogen.

4. A kit according to claim 1, wherein the units for use during the progestogenic phase do not contain a synthetic estrogen.

5. A kit according to claim 1, wherein the daily hormone units for use during the estrogenic phase contain the synthetic estrogen in an amount equivalent to 5-15 μ

g ethinyl estradiol.

6. A kit according to claim 1, wherein the daily hormone units for use during the progestogenic phase contain the biogenic estrogen in an amount equivalent to 1-3 mg 17beta-estradiol.

7. A kit according to claim 1, wherein the daily hormone units for use during the progestogenic phase contain the progestogen in an amount equivalent to 75-150 μ

g levonorgestrel.

8. A kit according to claim 1, wherein the synthetic estrogen is selected from the group consisting of:

ethinyl estradiol, mestranol, quinestranol, precursors capable of liberating such an estrogen when used in the present method and mixtures thereof.

9. A kit according to claim 1, wherein the biogenic estrogen is selected from the group consisting of:

estradiol, estrone, estran, estriol, estetrol, conjugated equine estrogens, precursors capable of liberating such an estrogen when used in the present method and mixtures thereof.

10. A kit according to claim 1, wherein the progestogen is selected from the group consisting of levonorgestrel, norgestimate, norethisterone, dydrogesterone, drospirenone, 3-beta-hydroxydesogestrel, etonogestrel, 17-deacetyl norgestimate, 19-norprogesterone, acetoxypregnenolone, allylestrenol, anagestone, chlormadinone, cyproterone, demegestone, desogestrel, dienogest, dihydrogesterone, dimethisterone, ethisterone, ethynodiol diacetate, flurogestone acetate, gastrinon, gestodene, gestrinone, hydroxymethylprogesterone, hydroxyprogesterone, lynestrenol, medrogestone, medroxyprogesterone, megestrol, melengestrol, nomegestrol, norethindrone, norethynodrel, norgestrel, norgestrienone, normethisterone, progesterone, quingestanol, (17alpha)-17-hydroxy-11-methylene-19-norpregna-4,15-diene-20-yn-3-one, tibolone, algestone acetophenide, nestorone, promegestone, 17-hydroxyprogesterone esters, 19nor-17hydroxyprogesterone, 17alpha-ethinyl-testosterone, 17alpha-ethinyl-19nor-testosterone, d-17beta-acetoxy-13beta-ethyl-17alpha-ethinyl-gon-4en-3-one oxime and precursors of these compounds.

11. A kit according to claim 1, wherein the hormone units for use during the estrogenic phase contain ethinyl estradiol or a combination of ethinyl estradiol and estradiol and/or precursors thereof in a therapeutically effective amount to inhibit ovulation and the hormone units for use during the progestogenic phase contain a combination of estradiol and/or a precursor thereof and a progestogen selected from the group consisting of levonorgestrel, norgestimate, norethisterone, drospirenone, dydrogesterone and their precursors, in a therapeutically effective amount to inhibit ovulation and to transform the endometrium from a proliferative into a secretory state.

12. A kit according to claim 1, wherein the plurality of daily hormone units consists of 1-18 units for use in the estrogenic phase and 10-27 units for use in the progestogenic phase.

14. A method according to claim 13, wherein the units for use during the estrogenic phase also contain a biogenic estrogen.

15. A method according to claim 13, wherein the units for use during the progestogenic phase do not contain a synthetic estrogen.

16. A method according to claim 13, wherein the daily hormone units for use during the estrogenic phase contain the synthetic estrogen in am amount equivalent to 3-40 μ

g ethinyl estradiol.

17. A method according to claim 13, wherein the daily hormone units for use during the progestogenic phase contain the biogenic estrogen in an amount equivalent to 0.5-5 mg 17beta-estradiol.

18. A method according to claim 13, wherein the daily hormone units for use during the progestogenic phase contain the progestogen in an amount equivalent to 30-750 μ

g levonorgestrel.

19. A method according to claim 13, wherein the synthetic estrogen is selected from the group consisting of:

ethinyl estradiol, mestranol, quinestranol, precursors capable of liberating such an estrogen when used in the present method and mixtures thereof.

20. A method according to claim 13, wherein the biogenic estrogen is selected from the group consisting of:

estradiol estrone, estran, estriol, estetrol, conjugated equine estrogens, precursors capable of liberating such an estrogen when used in the present method and mixtures thereof.

21. A method according to claim 13, wherein the progestogen is selected from the group consisting of levonorgestrel, norgestimate, norethisterone, dydrogesterone, drospirenone, 3-beta-hydroxydesogestrel, etonogestrel, 17-deacetyl norgestimate, 19-norprogesterone, acetoxypregnenolone, allylestrenol, anagestone, chlormadinone, cyproterone;

demegestone, desogestrel, dienogest, dihydrogesterone, dimethisterone, ethisterone, ethynodiol diacetate, flurogestone acetate, gastrinon, gestodene, gestrinone, hydroxymethylprogesterone, hydroxyprogesterone, lynestrenol, medrogestone;

, medroxyprogesterone, megestrol, melengestrol, nomegestrol, norethindrone, norethynodrel, norgestrel, norgestrienone, normethisterone, progesterone, quingestanol, (17alpha)-17-hydroxy-11-methylene-19-norpregna-4,15-diene-20-yn-3-one, tibolone, algestone acetophenide, nestorone, promegestone, 17-hydroxyprogesterone esters, 19-nor-17hydroxyprogesterone, 17alpha-ethinyl-testosterone, 17alpha-ethinyl-19-nor-testosterone, d-17beta-acetoxy-13beta-ethyl-17alpha-ethinyl-gon-4-en-3-one oxime and precursors of these compounds.

22. A method according to claim 13, wherein the hormone units for use during the estrogenic phase contain ethinyl estradiol or a combination of ethinyl estradiol and estradiol and/or precursors thereof in a therapeutically effective amount to inhibit ovulation and the hormone units for use during the progestogenic phase control a combination of estradiol and/or a precursor thereof and a progestogen selected from the group consisting of levonorgestrel, norgestimate, norethisterone, drospirenone, dydrogesterone and their precursors, in a therapeutically effective amount to inhibit ovulation and to transform the endometrium from a proliferative into a secretory state.

13. A contraceptive method that uses a plurality of hormone units and consists of two alternating consecutive phases—

an estrogenic and a progestogenic phase—

said method comprising administering to a female of childbearing capability

a) during the estrogenic phase one or more hormone units to provide a therapeutically effective amount of synthetic estrogen or a combination of synthetic estrogen and biogenic estrogen to inhibit ovulation and

b) during the progestogenic phase one or more hormone units to provide a combination of biogenic estrogen and progestogen in a therapeutically effective amount to inhibit ovulation and to transform the endometrium from a proliferative into a secretory state,

wherein the progestogenic phase encompasses a period of at least 10 days and the two consecutive phases together encompass a period of 20-35 days.